MECOM fusion partner and bone marrow blast percentage influence outcomes of patients with MECOM rearranged acute myeloid leukaemia.

MECOM rearrangements (MECOM-r) are acute myeloid leukaemia (AML)-defining, regardless of blast percentage or MECOM fusion partner. We sought to investigate if blast percentage or MECOM-r partner was associated with overall survival (OS). We included 152 adult patients with newly diagnosed MECOM-r and classified blast percentage into <20% or ≥20% and MECOM-r partner into classic (GATA2::MECOM) or variant (others). Thirty-one per cent had <20% blasts, with 69% having ≥20%; 57% had classic and 43% variant MECOM-r. Treatment was with intensive chemotherapy (IC) in 41% and low-intensity therapy (LIT) in 59%. Composite complete remission rates were similar between IC (50%) and LIT (48%, p = 0.99). The median OS was 17 months (95% confidence interval [CI], 12-not estimable [NE]) for <20% blasts, compared with 9 months (95% CI, 6-10) for ≥20% blasts (p < 0.01). On multivariate analysis, ≥20% blasts were associated with worse OS (hazard ratio [HR] 1.9, [95% CI, 1.2-3.2], p < 0.01), independent of age, MECOM-r partner, additional cytogenetic abnormalities, treatment intensity, addition of venetoclax and stem cell transplant (SCT). HR for IC was 2.0 (95% CI, 1.1-3.7, p = 0.03). In <20% blasts, variant MECOM-r was independently associated with a reduced hazard of death (HR 0.2 [95% CI, 0.1-0.8], p < 0.01). MECOM-r AML is a heterogenous entity; consideration should be given to LIT approaches.